Bolignano Davide, Coppolino Giuseppe, Campo Susanna, Aloisi Carmela, Nicocia Giacomo, Frisina Nicola, Buemi Michele
Department of Internal Medicine, University of Messina, Messina, Italy.
Am J Nephrol. 2007;27(4):373-8. doi: 10.1159/000103912. Epub 2007 Jun 13.
It is known that many tubular proteins are involved in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD), which causes 8-10% of the cases of end-stage renal disease (ESRD) worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli such as ischemia or toxicity. In the present study, serum and urinary NGAL levels were evaluated in 26 ADPKD subjects. Both levels were significantly higher in patients than in controls (sNGAL 174 +/- 52 vs. 50 +/- 27 ng/ml, p < 0.05; uNGAL 119 +/- 42 vs. 7 +/- 6 ng/ml, p < 0.005) and a close correlation was also found between these parameters and the residual renal function (sNGAL/GFR: r = -0.8, p = 0.006; sNGAL/Creatinine: r = 0.9, p = 0.007; uNGAL/GFR: r = -0.49, p < 0.05; uNGAL/Creatinine: r = 0.84, p < 0.001). Patients were further divided into two groups according to the cystic development assessed with echotomography; subjects with higher cystic growth (HCG) presented higher sNGAL and uNGAL levels with respect to others (sNGAL: 242 +/- 89 vs. 88 +/- 34 ng/ml, p < 0.05; uNGAL: 158 +/- 45 vs. 73 +/- 27 ng/ml, p < 0.05). The strict correlation between NGAL levels and residual renal function is perfectly in accord with recent studies on patients with other ESRD-associated diseases. We can hypothesize that tubular cells produce big quantities of NGAL as a consequence of increased apoptosis following chronic damage or as a compensatory response, similar to that observed in acute stress conditions (ischemia, toxicity ...). Finally, our last finding that patients with HCG showed higher levels of NGAL suggests that this protein could be also involved in the cyst growth process, as previously reported about epithelial and tumoral expansion.
已知许多肾小管蛋白参与常染色体显性多囊肾病（ADPKD）的发病机制，该病在全球范围内导致8%-10%的终末期肾病（ESRD）病例。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是一种在肾小管细胞上表达的蛋白质，其产生会因缺血或毒性等有害刺激而显著增加。在本研究中，对26名ADPKD患者的血清和尿液NGAL水平进行了评估。患者的这两种水平均显著高于对照组（血清NGAL：174±52 vs. 50±27 ng/ml，p<0.05；尿NGAL：119±42 vs. 7±6 ng/ml，p<0.005），并且还发现这些参数与残余肾功能之间存在密切相关性（血清NGAL/肾小球滤过率：r=-0.8，p=0.006；血清NGAL/肌酐：r=0.9，p=0.007；尿NGAL/肾小球滤过率：r=-0.49，p<0.05；尿NGAL/肌酐：r=0.84，p<0.001）。根据超声断层扫描评估的囊肿发育情况，将患者进一步分为两组；囊肿生长较高（HCG）的受试者相对于其他受试者呈现出更高的血清NGAL和尿NGAL水平（血清NGAL：242±89 vs. 88±34 ng/ml，p<0.05；尿NGAL：158±45 vs. 73±27 ng/ml，p<0.05）。NGAL水平与残余肾功能之间的紧密相关性与最近对其他ESRD相关疾病患者的研究完全一致。我们可以假设，由于慢性损伤后细胞凋亡增加或作为一种代偿反应，肾小管细胞会产生大量的NGAL，这与在急性应激条件下（缺血、毒性等）观察到的情况类似。最后，我们的最新发现表明，HCG患者的NGAL水平较高，这表明该蛋白可能也参与囊肿生长过程，正如先前关于上皮细胞和肿瘤扩张的报道。
